Leptomycin

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Leptomycin B is a secondary metabolite produced by Streptomyces spp.

Leptomycin B (LMB) was originally discovered as a potent anti-fungal antibiotic. Leptomycin B was found to cause cell elongation of the fission yeast Schizosaccharomyces pombe. Since then this elongation effect is being used for the bioassay of Leptomycin. However, recent data (2003) showed that Leptomycin causes G1 cell cycle arrest in mammalian cells and is a potent anti-tumor agent against murine experimental tumors

Therefore Leptomycin B became a potent and specific nuclear export inhibitor. Leptomycin B alkylates and inhibits CRM1 (chromosomal region maintenance)/exportin 1 (XPO1), a protein required for nuclear export of proteins containing a nuclear export sequence (NES). In addition to antifungal and antibacterial activities, Leptomycin B blocks the cell cycle and is a potent anti-tumor agent. At low nM concentrations, Leptomycin B blocks the nuclear export of many proteins including HIV-1 Rev, MAPK/ERK, and NF-κB/IκB, and it stabilizes the expression of p53. Leptomycin B also inhibits the export and translation of many RNAs, including COX-2 and c-Fos mRNAs, by inhibiting export of ribonucleoproteins.

Leptomycin A (LPA) was discovered together with LMB. LMB is twice as potent as LPA.

References

  • Hamamoto T, Seto H, Beppu T. Leptomycins A & B, new antifungal antibiotics. The Journal of Antibiotics. 1983, 36: 646-650.

External links

Original data copied with permission from Leptomycin B manufacturer product page (Fermentek)




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